No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis Academic Article uri icon

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abstract

  • In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD.

authors

  • Loley, Christina
  • Alver, Maris
  • Assimes, Themistocles L
  • Bjonnes, Andrew
  • Goel, Anuj
  • Gustafsson, Stefan
  • Hernesniemi, Jussi
  • Hopewell, Jemma C
  • Kanoni, Stavroula
  • Kleber, Marcus E
  • Lau, King Wai
  • Lu, Yingchang
  • Lyytikäinen, Leo-Pekka
  • Nelson, Christopher P
  • Nikpay, Majid
  • Qu, Liming
  • Salfati, Elias
  • Scholz, Markus
  • Tukiainen, Taru
  • Willenborg, Christina
  • Won, Hong-Hee
  • Zeng, Lingyao
  • Zhang, Weihua
  • Anand, Sonia
  • Beutner, Frank
  • Bottinger, Erwin P
  • Clarke, Robert
  • Dedoussis, George
  • Do, Ron
  • Esko, Tõnu
  • Eskola, Markku
  • Farrall, Martin
  • Gauguier, Dominique
  • Giedraitis, Vilmantas
  • Granger, Christopher B
  • Hall, Alistair S
  • Hamsten, Anders
  • Hazen, Stanley L
  • Huang, Jie
  • Kähönen, Mika
  • Kyriakou, Theodosios
  • Laaksonen, Reijo
  • Lind, Lars
  • Lindgren, Cecilia
  • Magnusson, Patrik KE
  • Marouli, Eirini
  • Mihailov, Evelin
  • Morris, Andrew P
  • Nikus, Kjell
  • Pedersen, Nancy
  • Rallidis, Loukianos
  • Salomaa, Veikko
  • Shah, Svati H
  • Stewart, Alexandre FR
  • Thompson, John R
  • Zalloua, Pierre A
  • Chambers, John C
  • Collins, Rory
  • Ingelsson, Erik
  • Iribarren, Carlos
  • Karhunen, Pekka J
  • Kooner, Jaspal S
  • Lehtimäki, Terho
  • Loos, Ruth JF
  • März, Winfried
  • McPherson, Ruth
  • Metspalu, Andres
  • Reilly, Muredach P
  • Ripatti, Samuli
  • Sanghera, Dharambir K
  • Thiery, Joachim
  • Watkins, Hugh
  • Deloukas, Panos
  • Kathiresan, Sekar
  • Samani, Nilesh J
  • Schunkert, Heribert
  • Erdmann, Jeanette
  • König, Inke R

publication date

  • December 2016